1c9w

CHO REDUCTASE WITH NADP+

spinqualitylabelsall models 1c9w, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1c9w is a 1 chain structure with sequence from Cho cell lines. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NAP Activity: Alcohol dehydrogenase (NADP(+)), with EC number 1.1.1.2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ALD2_CRIGR] Reductase with a preference for aliphatic substrates. Can also act on small aromatic aldehydes, steroid aldehydes and some ketone substrates. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Chinese hamster ovary (CHO) reductase is an enzyme belonging to the aldo-keto reductase (AKR) superfamily that is induced by the aldehyde-containing protease inhibitor ALLN (Inoue, Sharma, Schimke, et al., J Biol Chem 1993;268: 5894). It shows 70% sequence identity to human aldose reductase (Hyndman, Takenoshita, Vera, et al., J Biol Chem 1997;272:13286), which is a target for drug design because of its implication in diabetic complications. We have determined the crystal structure of CHO reductase complexed with nicotinamide adenine dinucleotide phosphate (NADP)+ to 2.4 A resolution. Similar to aldose reductase and other AKRs, CHO reductase is an alpha/beta TIM barrel enzyme with cofactor bound in an extended conformation. All key residues involved in cofactor binding are conserved with respect to other AKR members. CHO reductase shows a high degree of sequence identity (91%) with another AKR member, FR-1 (mouse fibroblast growth factor-regulated protein), especially around the variable C-terminal end of the protein and has a similar substrate binding pocket that is larger than that of aldose reductase. However, there are distinct differences that can account for differences in substrate specificity. Trp111, which lies horizontal to the substrate pocket in all other AKR members is perpendicular in CHO reductase and is accompanied by movement of Leu300. This coupled with movement of loops A, B, and C away from the active site region accounts for the ability of CHO reductase to bind larger substrates. The position of Trp219 is significantly altered with respect to aldose reductase and appears to release Cys298 from steric constraints. These studies show that AKRs such as CHO reductase are excellent models for examining the effects of subtle changes in amino acid sequence and alignment on binding and catalysis. Crystal structure of CHO reductase, a member of the aldo-keto reductase superfamily.,Ye Q, Hyndman D, Li X, Flynn TG, Jia Z Proteins. 2000 Jan 1;38(1):41-8. PMID:10651037 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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